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Citations to this article

Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype
Diane R. Bielenberg, … , Caroline Choi Kim, Michael Klagsbrun
Diane R. Bielenberg, … , Caroline Choi Kim, Michael Klagsbrun
Published November 1, 2004
Citation Information: J Clin Invest. 2004;114(9):1260-1271. https://doi.org/10.1172/JCI21378.
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Article Angiogenesis

Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype

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Abstract

Melanoma is the most lethal skin cancer. Most deaths from melanoma result from metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but the effects of semaphorins on tumor metastasis have not been documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human cell lines in vitro and in vivo, which suggested that it may be a metastasis inhibitor. Metastatic human melanoma cells were transfected with SEMA3F and implanted into mice; the resultant tumors did not metastasize. Rather, the primary tumors resembled benign nevi characterized by large areas of apoptosis, diminished vascularity, inhibition of hyperplasia in overlying epidermal cells, and encapsulated tumor borders delineated by thick layers of fibroblasts and collagen matrix. This phenotype is in stark contrast to highly invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The repulsive activity was abrogated by NRP2 RNA interference. Together these results indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and stromal cells and raise the possibility of SEMA3F having therapeutic potential.

Authors

Diane R. Bielenberg, Yasuhiro Hida, Akio Shimizu, Arja Kaipainen, Michael Kreuter, Caroline Choi Kim, Michael Klagsbrun

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Total
Citations: 4 2 4 4 3 4 4 3 6 3 7 12 7 11 8 8 10 6 6 2 2 116
Citation information
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Citations to this article in year 2017 (6)

Title and authors Publication Year
Methods in Molecular Biology
LT Alto, JR Terman
Methods in molecular biology (Clifton, N.J.) 2017
Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study
G Stallone, M Matteo, GS Netti, B Infante, AD Lorenzo, C Prattichizzo, S Carlucci, F Trezza, L Gesualdo, P Greco, G Grandaliano, C Oudejans
PloS one 2017
The Id-protein family in developmental and cancer-associated pathways
C Roschger, C Cabrele
Cell Communication and Signaling 2017
A quantitative method for screening and identifying molecular targets for nanomedicine
P Guo, J Yang, DR Bielenberg, D Dillon, D Zurakowski, MA Moses, DT Auguste
Journal of Controlled Release 2017
Refuting the hypothesis that semaphorin-3f/neuropilin-2 exclude blood vessels from the cap mesenchyme in the developing kidney: Sema3F and NRP2 In Kidney Development
DA Munro, P Hohenstein, TM Coate, JA Davies
Developmental Dynamics 2017
The crucial role of SEMA3F in suppressing the progression of oral squamous cell carcinoma
Y Liu, R Li, K Yin, G Ren, Y Zhang
Cellular & Molecular Biology Letters 2017

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